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Abstract

Kounis syndrome is characterized by hypersensitivity and coronary artery disorder due to various environmental exposures, drugs and proton pump inhibitors (PPIs). Vasospastic allergic angina, allergic myocardial infarction and stent thrombosis with occulting thrombus infiltrated by eosinophils and histamine liberated by recruited mast cells are all seen in Kounis syndrome.

Introduction

Kounis syndrome is characterized by hypersensitivity and coronary artery
disorder due to various environmental exposures, drugs and proton pump
inhibitors (PPIs). Vasospastic allergic angina, allergic myocardial
infarction and stent thrombosis with occulting thrombus infiltrated by
eosinophils and histamine liberated by recruited mast cells are all seen in
Kounis syndrome [1].

Case

On 21st January 2017 at 10.45 AM, a 52 year old female was brought by
relatives with complaints of sudden onset itching all over the body,
including palms and soles within 20 minutes of oral consumption of tablet
40 mg patoprazole. She had had an episode of giddiness, blackout, and she
had collapsed in the bath room and suffered from urticaria all over the
body. On arrival to the hospital, her pulse and blood pressure were not
recordable, her extremities were cold and there was puffiness of the face,
and congestion of the conjunctivae (Figure 1). She was put on a multipara
Cardiac noninvasive blood pressure monitor. Her Blood pressure was
65/42 MM Hg recorded by non-invasive method. Her heart rate was 120
beats per minute and oxygen saturation was 88%. There is no past history
of allergy, bronchial asthma or hay fever. She was complaining of a
burning sensation in the chest, for which her family doctor had prescribed
pantaprazol. She denied any history of consumption of NSAID. She was a
known case of hypothyroidism and hypertension. She had been taking
levothyroxine 88 microgram on empty stomach daily, amlopine 5 mg and
metaprolol 50 mg for the past 8 years.

With us, she was given a head low position, nasal oxygen at 4 liters per
minute and intravenous crystalloid solution @ 20 ml/kg over one hour
followed by 15 ml/per hour over the next two hours, followed by 10ml/kg
for the next four hours. Intravenous methyl prednisolone 1000 mg in 250
ml of normal saline over 60 minutes was administered along with 45.5 mg
chlorphenaramine maleate by slow intravenous route. Her blood pressure
and pulse rate gradually improved to 114/64 and 88 per minute.
Extremities became warm. She had passed 580 ml urine in the last 6 hours.
Urticaria, conjunctivae congestions, edema of body reduced at the end of 9
hours (Figure 2). Details of improvement of pulse, blood pressures etc…
are shown in figure (Figure 3). Patient felt comfortable. Edema of body
and face reduced (Figure 2).

Figure 2: Complete recovery.

Figure 3: Pulse, blood pressure recovery.

Electrocardiogram on admission showed a heart rate of 103 per minute, 4
mm ST segment depression in leads II,III,AVF, V3-V6, a small q wave,
ST segment elevation and T wave inversion in AVL (Figure 4) suggestive
of right coronary involvement. Subsequent ECG at the end of 8 hours of
admission showed that ST segments returned to normal with a heart rate
of 71 beats per minute Figure (Figure 4).

Figure 4: ECGa ST depression in lead II, III, AVF, V2-V6.

Her hemoglobin was 10.1 gms/dl, white cells count was 8400 per cu mm,
platelets 232000/cu.mm, random blood sugar 171.6 mg/dl, liver function
and renal functions tests were normal. Serum IgE was 386.53 IU/ml (normal 3-188 IU/ml). Troponin T test was negative and other cardiac
enzymes were within normal limits. Lastly she was seen on 23/6/2017
with no complaints and a normal blood pressure and ECG. Patient and
relatives denied for sensitivity skin chest or oral challenge for available
proton pump inhibitors (PPIs).

Discussion

H2 receptor antagonists (cimetidine and ranitine) and Proton pump
inhibitor like omeprazole, esomeprozole, rabeprazole, lansoprozole and
pantoprozole, are commonly used medications for the treatment of acid
peptic disease and gastro esophageal reflux disease. The five PPIs don’t
share the same chemical structure; hence indicate that a person who is
allergic to one PPI might tolerate other PPIs. However cross reactivity of
PPIs, have been found that people allergic to omeprazole are frequently
allergic to pantoprozole and vice versa [1,2]. PPI’s have been reported to
cause an immunoglobulin (IgE) hypersensitivity reaction [3]. IgE plays an
important role in the development of severe anaphylaxis to PPIs, as in the
present case [3].

Kounis syndrome is characterized by hypersensitivity coronary disorder to
various environmental exposures, drugs and PPIs. Vasospastic allergic
angina, allergic myocardial infarction and stent thrombosis with an
occulting thrombus, infiltrated by eosinophils and histamine liberation by
recruited mast cells are all features of Kounis syndrome [4]. In 1998,
Brunwald E categorized allergic angina due to allergic reactions with
mediators such as histamines or leukotriens acting on the vascular smooth
muscles that can induce a vasospastic angina [5]. Kounis syndrome is
caused by inflammatory mediators such as histamine, platelet-activating
factor, archidonic acid products, neutral proteases, a variety of cytokines
and chemokines released during the allergic process [4].

Three variants of kounis syndrome have been described [4]. The present
case describes a type I variant which includes normal or nearly normal
coronaries without any predisposing factors for coronary artery disease in
whom the acute liberated inflammatory mediators can induce a coronary
spasm with ST depression (Figure 4) without increase of cardiac enzymes
and tropinin. Complete recovery of ST-T changes confirmed that changes
were secondary to the allergic reaction to PPI. Kounis syndrome type I
variant responds to intravenous methyl prednisolone. We avoided
epinephrine; which is the drug of choice in anaphylaxis, because in
Kounis syndrome it can aggravate ischemia and worsen the coronary
vasospasm. However epinephrine action is blunted in this case as the
patient is taking beta-blocker [4]. In the present case IgE induced
anaphylaxis was evoked by oral pantaprazole. Kounis syndrome type II is
characterized by the rupture or erosion of the existing coronary plug
resulting in acute myocardial infarction. Type III includes stent thrombosis
with re-infraction [4]. In a histopathology study, the victim died of kounis
syndrome where the Coronary artery intima, media and adventitia were
infiltrated by eosinophils and mast cells [4].

PPI’s are common routinely prescribed drugs, which are easily available
even without prescriptions. Though rarely they evoke life threatening
anaphylaxis, health professionals need to be aware of this possibility.
However an oral challenge, performed under medical supervision, should
be performed with non-cross reacting PPIs to ensure that it is safety
tolerated.

Acknowledgement

We are grateful to Dr Punishi Parekh Resident in pediatric KEM and G.S.
Medical College Mumbai for editing the case report.